NY Prostate Cancer Conference - K. Touijer - Session 4: Predicting clinical and biochemical endpoints before surgery

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NY Prostate Cancer Conference - K. Touijer - Session 4: Predicting clinical and biochemical endpoints before surgery

  1. 1. Predicting Clinical and Biochemical Endpoints Before Surgery Karim Touijer, MD Department of Surgery, Urology Service Memorial Sloan-Kettering Cancer Center
  2. 2. <ul><li>“ Chance is an illusion…, nothing happens by chance” </li></ul><ul><li>The Doctrine of Chances </li></ul><ul><li>By Abraham de Moivre </li></ul>
  3. 3. Determinism Pierre Simon Laplace “ Given for one instant an intelligence which could comprehend all the forces by which nature is animated and the respective situation of the beings who compose it – an intelligence sufficiently vast to submit these data to analysis- it would embrace in the same formula the movements of the greatest bodies of the universe and those of the lightest atom; for it, nothing would be uncertain and the future, as the past, would be present to its eyes”
  4. 4. Endpoints <ul><li>Death from cancer </li></ul><ul><li>Development of metastases </li></ul><ul><li>Biochemical recurrence </li></ul>
  5. 5. Established Clinical Factors that Characterize Prostate Cancer <ul><li>Cancer Volume: </li></ul><ul><li>PSA </li></ul><ul><li>Bx data </li></ul><ul><li>Imaging </li></ul><ul><li>Cancer Aggressiveness: </li></ul><ul><li>Gleason Grade </li></ul><ul><li>Extent of Cancer: </li></ul><ul><li>Clinical stage </li></ul><ul><li>Imaging </li></ul>Each of these clinical prognostic factors (T-stage, grade, PSA) independently predicts pathologic stage and prognosis after treatment.
  6. 6. NOMOGRAM FOR PREDICTING PATHOLOGIC STAGE PSA 4.1- 10 PSA 10.1-20 Gleason Sum Clinical Stage Clinical Stage 5 69 38 23 57 28 16 (63-74) (32-45) (13-38) (50-64) (22-34) (8-28) T1c T2b T3a T1c T2b T3a Organ-Confined Johns Hopkins, Baylor, U. Michigan SPOREs 7 48 21 11 36 14 7.2 (42-53) (17-25) (5.8-20) (30-42) (11-18) (4-14) Modified from Partin AW, Kattan MW, Subong ENP, Walsh PC, Wojno KJ, Oesterling JE, Scardino PT, Pearson JD. JAMA 1997; 277:1445.
  7. 7. MSKCC web site nomogram software program: algorithm for prognosis and pathologic stage <ul><li>Includes pretreatment and postoperative predictions. Uses published prostate cancer nomograms. </li></ul>Available at http://www.mskcc.org/prostate/nomograms
  8. 8. Progression-free probability by risk group * p < 0.05 Mod. From D’Amico et al JAMA 280:969-74, 1998 * * * High risk Intermediate risk Low risk T1c/T2a, Gl 2-6, PSA <10 T2b or Gl 7 or PSA 10-20 T2c or Gl 8-10 or PSA >20
  9. 9. Improving prediction of stage means better design of the surgical treatment strategy
  10. 10. When and to what anatomical extent should we perform a pelvic lymph node dissection?
  11. 12. J Urol. 2010 Jul; 184(1): 143-8.
  12. 13. MSK data
  13. 14. What is the risk of EPE and to what extent can we safely preserve the NVB?
  14. 15. NVB intra-fascial dissection
  15. 16. NVB Inter-Fascial Dissection
  16. 17. NVB Resection - Extrafascial
  17. 18. Should the established prognostic indicators be updated ?
  18. 19. <ul><li>Upgrading </li></ul><ul><li>Tertiary </li></ul><ul><li>Interobserver variability </li></ul>Gleason Grading
  19. 20. Tradeoff: avoiding PLND in selected patients misses a proportion of nodal metastases (n=5510) Nomogram LND Avoided % of +LN Prediction % no PLND TN FN undetected NPV < 1% 2.3 125 2 0.97 .984 < 2% 43.8 2386 25 12.1 .990 < 3% 66.8 3623 56 27.2 .985 < 4% 76.0 4110 77 37.4 .982 < 5% 82.8 4466 94 45.6 .979 TN = true negative NPV = negative predictive value FN = false positive
  20. 21. <ul><li>Based on this cohort of 2200 patients— </li></ul><ul><li>If had used Gl <= 6 as exclusion criteria for PLND and : </li></ul><ul><ul><li>Utilized outside Gleason score </li></ul></ul><ul><ul><ul><li>793 pts (36%) would have undergone PLND </li></ul></ul></ul><ul><ul><li>Utilized reviewed Gleason score </li></ul></ul><ul><ul><li>903 pts (41%) would have undergone PLND </li></ul></ul><ul><li>Of additional 110 PLND performed based on path review, nodal metastasis in 10 </li></ul>Biopsy Gleason upgrading by a tertiary referral center is associated with increased incidence of lymph node involvement. Implications for pelvic lymphadenectomy decision models Sharp DS, Touijer K, Eastham JA, Scardino PT, and Guillonneau B
  21. 22. PSA <ul><li>PSA measured with the ‘WHO’ standardized assays are 22-25% lower than those measured with ‘Hybritech’ standardized assays </li></ul><ul><ul><li>PSA-Hyb 4.0 = PSA-WHO 3.1 </li></ul></ul><ul><ul><li>PSA-Hyb 2.5 = PSA-WHO 2.0 </li></ul></ul><ul><li>Use of PSA-WHO will underestimate cancer risk and will lead to missed cancers </li></ul><ul><li>Results from risk prediction tools will be artificially lower </li></ul>
  22. 23. Which standard are the manufacturers using? MANUFACTURER: Instrument/Assay CALIBRATION Abbott IMx / AxSYM/ AxSYM Plus / ARCHITECT WHO Biomerieux VIDAS WHO Roche Elecsys / Cobas / Modular Analytics WHO Siemens Dimension / ADVIA Centaur / Immulite WHO Immulite 3 rd gen Hybritech TOSOH AIA Hybritech Ortho Clinical Diagnostics VITROS Hybritech Beckman Coulter Access / UniCel Both
  23. 24. Age (1) (2) (3) (4) (5) (6) (7)=(3)x(5)x(6) (8)=(4)x(5)x(6) (9)=(7)-(8) No. of men with PSA > 4.0 ng/ml No. of men in (1) and (2) with biopsy-detectable cancer Proportion with PSA test in past year (%) Proportion complied with biopsy (%) No. of biopsy detectable cancers No. of cancers missed Hybritech WHO Hybritech WHO Hybritech WHO 40-44 46490 15980 20010 8250 7 60 820 340 480 45-49 148380 77250 68860 41950 9 60 3900 2380 1520 50-54 340130 167450 157940 88490 16 55 13970 7830 6140 55-59 292050 171870 134600 86790 24 55 17610 11360 6250 60-64 434690 227440 186960 108230 31 50 28980 16780 12200 65-69 430440 289260 202720 149090 34 40 27270 20060 7210 70-74 660540 459840 309660 233920 33 30 30310 22890 7420 75-79 533720 245660 232430 125020 35 20 16380 8810 7570 80-84 646130 435780 312140 231260 39 15 18080 13400 4680 Total 3532570 2090530 1625320 1073000 20% 36% 157320 103850 34%
  24. 25. Shift in Stage at Diagnosis after Introduction of PSA (SEER Data) 90 5 5 Local Regional Distant 1995 Percent Percent 68 13 19 0 20 40 60 80 100 Local Regional Distant 1983 0 20 40 60 80 100
  25. 26. Clinical Stage <ul><li>The majority are cT1c </li></ul><ul><li>PSA , Bx Gleason and % positive Bx cores are strong predictors of BCR after RP </li></ul><ul><li>Cooperberg et al. J.Urol.2005; 173:1938 </li></ul><ul><li>Stephenson et al. j Natl Cancer Inst. 2006;98:175 </li></ul>Is Clinical stage of a limited usefulness in predicting pathological outcomes and BCR after radical prostatectomy?
  26. 27. Minimal Impact of Clinical Stage on Prostate Cancer Prognosis Among Contemporary Patients with Clinically Localized Disease Reese et al. J Urol. 2010; 184:114 AIC unchanged whether the model included clinical stage or not Clinical Stage EPE Positive margins cT1c reference reference cT2a 1.09 (0.89-1.33) 0.89 (0.74-1.08) cT2b 1.55 (1.17-2.06)* 1.16 (0.88-1.53) cT2c 1.37 (1.12-1.68)* 1.05 (0.86-1.27) Clinical Stage p Value cT1c reference reference cT2a 1.05 (0.84-1.23) 0.66 cT2b 1.24 (0.95-1.62) 0.11 cT2c 0.9 (0.72-1.13) 0.36
  27. 28. <ul><li>Armatys et al . Is it necessary to separate T1c from T2 prostate adenocarcinoma? BJU Int 2005; 96:777. </li></ul><ul><li>Billis et al . Are Prostate Clinical T1c and T2 similar? Int Braz J. Urol. 2006; 32:165 </li></ul><ul><li>Ghavamian et al. Comparison of clinically nonpalpable PSA detected (cT1c) versus palpable (cT2) prostate cancers in patients undergoing radical retropubic prostatectomy. Urology 1999; 54:105. </li></ul>cT1 vs cT2 poor correlation with BCR
  28. 29. Biopsy Gleason Grade  2+  2 3+3  3+  4  2+3  4+  Total Points 0 20 40 60 80 100 120 140 160 180 200 60 Month Rec. Free Prob. .96 .93 .9 .85 .8 .7 .6 .5 .4 .3 .2 .1 .05 3+  2 Clinical Stage T1c T1ab T2a T2c T3a T2b Points PSA 0.1 1 2 3 6 8 9 10 12 16 30 45 70 110 7 20 4 Preoperative Nomogram for Prostate Cancer Recurrence Instructions for Physician : Locate the patient’s PSA on the PSA axis. Draw a line straight upwards to the Points axis to determine how many points towards recurrence the patient receives for his PSA. Repeat this process for the Clinical Stage and Biopsy Gleason Sum axes, each time drawing straight upward to the Points axis. Sum the points achieved for each predictor and locate this sum on the Total Points axis. Draw a line straight down to find the patient’s probability of remaining recurrence free for 60 months assuming he does not die of another cause first. Note: This nomogram is not applicable to a man who is not otherwise a candidate for radical prostatectomy. You can use this only on a man who has already selected radical prostatectomy as treatment for his prostate cancer. Instruction to Patient : “Mr. X, if we had 100 men exactly like you, we would expect between <predicted percentage from nomogram - 10%> and <predicted percentage + 10%> to remain free of their disease at 5 years following radical prostatectomy, and recurrence after 5 years is very rare.” <ul><li>  1997 Michael W. Kattan and Peter T. Scardino </li></ul>Kattan MW et al: JNCI 1998; 90:766-771. Nomogram 0 10 20 30 40 50 60 70 80 90 100
  29. 30. Endorectal Magnetic Resonance Imaging (erMRI) Axial MRI Whole-mount prostate cancer cancer Normal Peripheral Zone

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